fibromuscular dysplasia support, education & advocacy
Fibromuscular dysplasia (FMD) is a complex disease that is most commonly seen in women, with systemic presentation that may include dissection or aneurysm most commonly in the renal and carotid arteries, low bone density, joint laxity, degenerative disease in the spine, migraine-like headaches, dizziness, and tinnitus. FMD is considered a rare disease; however, it is also believed to be underdiagnosed.

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Connections Between Fibromuscular Dysplasia and Spontaneous Coronary Artery Dissection

Recent studies have linked two rare conditions, fibromuscular dysplasia and spontaneous coronary artery dissection.

FMD and SCAD are most commonly seen in women. FMD's presentation may include dissection or aneurysm most commonly in the renal and carotid arteries, migraine-like headaches, dizziness, and tinnitus. SCAD occurs when the inner layer of an artery tears, creating a blood clot or blockage that results in acute coronary syndrome, heart attack or sudden death. 

According to research presented at the First International FMD Research Network Symposium held at Cleveland Clinic this May, more than 40 to 50 percent of SCAD patients may also have FMD, though the prevalence is uncertain at this time, said Dr. Sharonne Hayes, who directs and practices at the Women's Heart Clinic at Mayo Clinic in Rochester, Minnesota. Research shows that SCAD patients also diagnosed with FMD are at an increased risk for dissections in many arterial beds. 

SCAD may occur with little warning. Some patients report high levels of emotional stress or physical exertion prior to experiencing a dissection, Hayes said, but for many others the cause is unclear. Research indicates FMD may be a causative factor, yet a relationship between the severity of FMD and an occurrence of SCAD has not been determined. Patients may present with minimal evidence of FMD found through only through imaging, or patients may present with bruits, a sound heard within an artery as blood rushes by an obstruction, or symptomatic extracoronary aneurysms or dissections. Recommendations are for symptomatic patients or those with a family history suggestive of significant vascular events to undergo CT angiography from neck to pelvis with additional intracranial imaging if necessary. 

Dr. Jacqueline Saw of Vancouver General Hospital reported the first case study of SCAD and concomitant coronary FMD in Circulation earlier this year. "Although not all SCAD patients have CFMD, it is important to exclude FMD, as involvement of other vascular territories have long-term consequences," the article states.

SCAD research is shaping FMD experts' knowledge of the disease and patient evaluation.

In 2002, the U.S. Preventive Services Task Force began recommending that patients at high risk of developing cardiovascular disease — acute coronary syndrome or thrombotic cerebral vascular disease — take low-dose aspirin as a primary preventative. This year the Federal Drug Administration has come out against the therapy for the prevention of heart attack or stroke; however, aspirin still is recommended for as a preventative for patients who have experienced a prior event.

The treatment presents a complex risk-benefit analysis. There is evidence to support the recommendation of up to 81 mg of aspirin daily for patients diagnosed with cerebrovascular FMD, regardless of symptoms, reported Dr. Jeffrey Olin, Director of Vascular Medicine and the Vascular Diagnostic Laboratory in the Zena and Michael A. Wiener Cardiovascular Institute and Marie-Josée and Henry R. Kravis Center for Cardiovascular Health of The Mount Sinai Medical Center, during the International FMD Research Network Symposium. Aspirin's use in renal FMD patients is less clear, Olin said. 

"There is no evidence that aspirin prevents SCAD, and it should not be used for primary prevention in women, whose bleeding risk from aspirin is higher than men, and in the case of an undiagnosed cerebral aneurysm in an FMD patient could be catastrophic," Hayes said. 

Given these recent findings, FMD Chat is collaborating with the SCAD Alliance to provide more information about the diseases' overlaps. 


Newly Published Research Sheds Light on Possible Treatments for FMD

FMD Chat is pleased to be able to share excerpts from research just published in the Federation of American Societies for Experimental Biology Journal: Clinical and biochemical profiles suggest fibromuscular dysplasia is a systemic disease with altered TGF-B expression and connective tissue features, by Santhi Ganesh, Rachel Morissette, Zhi Xu, Florian Schoenhoff, Benjamin F. Griswold, Jiandong Yang, Lan Tong, Min-Lee Yang, Kristina Hunker, Leslie Sloper, Shinie Kuo, Rafi Raza, Dianna M. Milewicz, and Nazli B. McDonnell.

"Virtually no new information on FMD pertaining to mechanisms of disease has been published in the last 4 decades (5). Currently there is no medical therapy aimed at preventing progression or treating the underlying vascular pathology. Furthermore, there are no biomarkers or defined clinical features to identify who is at risk or who has the disorder... We undertook a deep phenotyping study of 47 individuals with FMD to evaluate relevant genetic, clinical, and anatomic features of this vascular disease...

Recent data have suggested that FMD represents a systemic vasculopathy, with the finding of a clinical manifestation of the disease in multiple arterial beds in at least one-third of patients (20). However, systematic evaluation for clinical and musculoskeletal features has not previously been performed. Our results indicate that FMD is a systemic disease with clinical features that extend beyond arterial pathology to include low bone density, joint laxity, and degenerative disease in the spine. The major clinical manifestations of FMD in our study are related to the vascular pathology and pain often related to early onset arthritis and degenerative joint disease in the spine...

The demographics and clinical histories of our subjects closely align with a U.S. registry of 447 patients with FMD (20) despite differences in study methodologies. We also are aware of 12 subjects enrolled in our cohort who are also enrolled in the same U.S. registry. Similar features included percentage of female sex (91.5 vs. 91.0%), mean age at presentation (44 vs. 47 yr), prevalence of hypertension (66.0 vs. 72.0% at study enrollment), headache (53.2 vs. 60.0%), current or former history of smoking (38.3 vs. 37.2%), and a history of exogenous hormone use (61.7 vs. 69.6%). However, in our study, 21.3% of our subjects had undergone surgical treatment for FMD with histopathologic confirmation, in contrast to 3.3% in the U.S. registry. A higher proportion of our cohort had experienced experienced a cerebrovascular event (48.9%) as compared to the U.S. registry, which noted TIA in 8.7% and stroke in 6.9% of its participants. This may reflect an ascertainment bias for patients who are more severely affected in being motivated to undertake the travel requirements for participation at the NIH. Our cohort did not include any individuals with asymptomatic disease discovered incidentally, whereas the U.S. registry included 5.6% with no symptoms or signs. In our study, surveillance MRA imaging of the entire arterial tree showed that 53.2% of our study subjects had vascular disease (aneurysm, beading, stenosis, or dissection) involving more than or equal to 2 arterial beds. Multiple vascular bed involvement was noted in 26.0–35.3% of patients with FMD in the U.S. registry who had imaging performed on additional arterial territories as clinically necessitated. Several caveats to the interpretation of our study MRA findings include that motion artifact from breathing is generally problematic for abdominal studies, previously treated arterial beds in cases of prior surgery or stent implantation could not be assessed, and we were unable to study every subject in the cohort because of contraindications to MR and/or gadolinium contrast administration. These caveats may have led to underestimating the severity and burden of systemic disease. Brain MR imaging is less susceptible to motion artifact, and we found that 12.8% of subjects had an intracerebral aneurysm. In the U.S. registry, 9 of 76 (11.8%) individuals with imaging data had a cerebral artery aneurysm, and 16 of 76 (21.1%) had carotid artery aneurysm, including both extracranial and intracranial internal carotid artery. Overall, the close alignment of demographic variables in our study as compared to the U.S. registry indicates that our cohort is a representative sample of U.S. patients with FMD, but likely with more severe clinical disease...

These findings have potential clinical implications. Our data suggest that an evaluation of degenerative spine arthritis and bone density may be helpful in identifying the cause and possible therapies for musculoskeletal symptoms. The yield of genetic testing for currently known connective tissue dysplasias in the FMD population is low in the absence of features that would otherwise indicate specific genetic testing, consistent with another published study (21). Given the rapid evolution of our understanding of vascular genetic diseases, formal genetic evaluation of patients with connective tissue features may be helpful to rule out other potentially overlapping disorders where FMD can be seen, such as vascular or type IV EDS. Finally, anecdotal evidence supports the rationale for therapy for FMD with pharmacologic agents that are known to decrease vascular TGF-B expression; (48) however, it is premature to make this treatment recommendation without a clinical trial. Further studies to identify the underlying molecular defect in FMD will be needed to clarify these issues."

The full text of this article is available for purchase from The FASEB Journal.


Rare Disease Community Petitions Federal Government for Research Reinstatement

On Feb. 28, 2014, Rare Disease Day, FMD Chat's CEO/Chairman & Founder, Sarah E. Kucharski, and Patient Advisory Panel member, Fran Saplis, delivered a petition with more than 10,000 signatures and 16 supporting organizations to Dr. Francis Collins, director of the National Institutes of Health. The petition called for the reinstatement of research into connective tissue diseases, and the rare disease community's efforts to bring the study back resulted in a feature story on page A5 of The Wall Street Journal on March 20. The community now awaits an answer from Collins. 

Below is the letter Kucharski included with the petition. 


Only through research will the medical community come to understand rare diseases like my own, fibromuscular dysplasia. In the fall of 2013, the National Institutes of Health cut a study headed by National Institute of Aging researcher Dr. Nazli McDonnell. The cut was made without warning and without satisfactory explanation to the patients involved. I was one such patient.

Although rare disease patients are champions of hope, I have little hope of a cure within my lifetime. Instead I hope that my contributions to research will help the patients who come after me. Like the patients diagnosed with the rare diseases addressed in this study, my hope suffers. Too little research is being done to cut projects — particularly those that are close to providing publishable conclusions. Such cuts impact the rare disease community as a whole.

“ I think of the rare disease problem as a giant jigsaw puzzle with 6000 pieces (the number of diseases). They are all related, but we don't yet for the most part know how,” Dr. Christopher Austin, director of the National Center for Advancing Translational Sciences (NCATS), part of the NIH, said in a December 2013 online conversation with Wall Street Journal reporter Amy D. Marcus.

So little known means there is so much to learn. Research into rare diseases also provides insight into more common diseases, making the return on investment that much greater. However, patients like me, patients who have invested limited time, energy, and resources into making themselves available to research only to see that research cut will come to learn that the NIH does not consider making a return on these patients’ investments worthwhile, and research participation will suffer.

The study I reference, project number NIA Protocol 2003-086 “Clinical and Molecular Manifestations of Heritable Disorders of Connective Tissue," aimed “to investigate cardiovascular, neurologist, pulmonary, and musculoskeletal disease, and pain and quality of life issues and Marfan, Ehlers-Danlos, Stickler syndromes and in closely related disorders that are collectively termed hereditary disorders of connective tissue. This study may lead to better medical care for patients with hereditary disorders of connective tissue."

The study featured a longitudinal arm and a mutational analysis arm. About 450 people were to be part of the longitudinal arm; another 1,385 enrolled in the mutational arm, and 2,000 people contributed samples to the National Human Genome Research Institute at the National Institutes of Health that would be analyzed under this study. A substudy was “to help investigators learn more about how genes affect the development and/or management of heritable disorders of connective tissue, such as Ehlers-Danlos, Stickler, Marfan Syndrome or an Overlap Connective Tissue Disorder."

Preliminary findings indicated that several patients had a family history of early death due to vascular events and “treatment with losartan or other angiotensin receptor blockers that modulate the pathway may be of benefit in the treatment of patients suffering from FMD” — patients like me. As is common with rare diseases, FMD has no treatment. Doctors do their best with limited knowledge to manage symptoms and surgically repair vascular damage. It took 31 years and a history of renal, celiac, and mesenteric bypass; bypass failure; kidney loss; four cerebral aneurysms; and a gastric rupture before I even achieved a diagnosis.

With this petition, signed by more than 10,000 people, I implore the NIH to reinstate NIA Protocol 2003-086 “Clinical and Molecular Manifestations of Heritable Disorders of Connective Tissue” such that the years of research, patient investment, and taxpayer dollars do not go to waste. Bring the study to completion and conclusions to publication. Do not compound rare disease patients’ suffering by casting aside the work that keeps hope alive and perhaps even some of us.

The petition, which patient advocate Kari Ulrich initiated and championed, is still collecting signatures. To lend your support to the cause, click here